This program encompasses a laboratory and clinical research program aimed at clarifying the mechanisms involved in heart attack (acute myocardial infarction) and ischemia (inadequate coronary blood flow) in man and experimental models, with the goal of providing a better understanding of the natural history and the effects of medical and surgical therapy in patients with coronary heart disease. The approaches employed include biochemical studies, acute experiments in a variety of animal preparations, studies on ischemia and infarction and their treatment in chronically instrumented, unanesthetized animals and in subhuman primates, and investigations in patients with ischemic heart disease. Clinical projects will focus particularly on prediction and reduction of risk after heart attack, exercise testing using vectorcardiographic and radionuclide methods, new radionuclide techniques for studying regional function and perfusion, and the effects of vasodilators in heart failure. Laboratory projects are concerned with animal models for angina pectoris and its treatment, effects of exercise on coronary collateral development, use of mitochrondrial enzymes. Both the clinical and laboratory research programs will bring hemodynamic and radiographic methods, nuclear techniques, echocardiography, implanted ultrasonic devices, telemetry, histology, basic biochemical measurements, and new statistical techniques to bear on the solution of these problems.